Viral Oncoproteins as Probes for Tumor Suppressor Function (original) (raw)
Related papers
Oncogenes and Tumor Suppressor Genes
Acta Oncologica, 1988
The artificial selection of the directly acting or acute RNA tumor viruses for high transforming ability has led to the isolation of defective retroviral genomes that have picked up, by accidental recombination, some of the important genes that influence, trigger or regulate cell division. These genes belong to at least four functionally different groups. Each of them can contribute to tumor development and/or progression after activation by structural or regulatory changes. Growth factor genes may act as oncogenes following constitutive activation in a cell that normally responds to, but does not produce, the corresponding growth factor (the autocrine model, exemplified by sis). Growth factor receptors may be fixed in a state of continuous, faulty signalling by the truncation of their external, ligand binding portion (examples: erb-B, fms). Genes coding for proteins involved in signal transduction may be activated by point mutations in certain, important domains (example: the ras-family). DNA binding proteins, presumably involved in DNA replication may drive cell division after constitutive activation by retroviral insertion, chromosomal translocation or gene amplification (example: the mycfamily).
Molecular Mechanisms Associated with Virus-induced Oncogenesis and Oncolysis
Cancer Research Journal
Cancer is a leading cause of human deaths worldwide. Besides inherited genetic disorders, a diverse range of physical, chemical and biological agents may induce cancer. About 15-20% of cancers are known to be originated due to pathogens. Viruses are considered to be the second (after smoking) most important risk factor in inducing human cancer. Viruses may either harbour a copy of oncogene or have an ability to alter the expression of cellular copy of the oncogenes. Both RNA and DNA viruses are can induce oncogenesis. Most of the DNA tumour viruses either integrate their genome (complete or part of it) into the host genome or express early genes that are required for early event of virus replication. These early genes are responsible for oncogenic transformation of host cells. Based upon the mechanism involved, oncogenic RNA viruses are divided into two groups-transforming and non-transforming RNA viruses. Transforming RNA viruses carry viral oncogenes that are homologous to the host oncogene, their expression in infected cells results in oncogenic transformation of the cell. Non-transforming RNA viruses induce oncogenesis similar to the DNA viruses. Contrary, oncolytic viruses selectively replicate in cancerous cells and induce cell death without any damage to the normal tissues. Typically, oncolytic viruses are nonpathogenic to humans that can naturally replicate in cancer cells by exploiting oncogenic cell signalling pathways. Pathogenic viruses can also be genetically manipulated which allow them to replicate in cancerous but not in normal cells. This review review describes the molecular mechanisms associated with virus induced oncogenesis and oncolysis.
Oncogene, 2010
Replication-competent oncolytic viruses hold great potential for the clinical treatment of many cancers. Importantly, many oncolytic virus candidates, such as reovirus and myxoma virus, preferentially infect cancer cells bearing abnormal cellular signaling pathways. Reovirus and myxoma virus are highly responsive to activated Ras and Akt signaling pathways, respectively, for their specificity for viral oncolysis. However, considering the complexity of cancer cell populations, it is possible that other tumorspecific signaling pathways may also contribute to viral discrimination between normal versus cancer cells. Because carcinogenesis is a multistep process involving the accumulation of both oncogene activations and the inactivation of tumor suppressor genes, we speculated that not only oncogenes but also tumor suppressor genes may have an important role in determining the tropism of these viruses for cancer cells. It has been previously shown that many cellular tumor suppressor genes, such as p53, ATM and Rb, are important for maintaining genomic stability; dysfunction of these tumor suppressors may disrupt intact cellular antiviral activity due to the accumulation of genomic instability or due to interference with apoptotic signaling. Therefore, we speculated that cells with dysfunctional tumor suppressors may display enhanced susceptibility to challenge with these oncolytic viruses, as previously seen with adenovirus. We report here that both reovirus and myxoma virus preferentially infect cancer cells bearing dysfunctional or deleted p53, ATM and Rb tumor suppressor genes compared to cells retaining normal counterparts of these genes. Thus, oncolysis by these viruses may be influenced by both oncogenic activation and tumor suppressor status.
Viral oncoprotein binding to pRB, p107, p130, and p300
Virus Research, 1995
The purpose of this review is to bring attention to some additional work in the tumor virus/ tumor suppressor field which may have been overshadowed by reports describing adenovirus, SV40, and HPV oncoprotein binding to pRB and ~53. The data reviewed herein provide further support for the model that a common mechanism by which DNA tumor viruses transform cells involves inactivation of cellular proteins which function as negative regulators of cell growth.
Human oncogenic viruses and cancer
The role of viral infection in cancer was established towards the beginning of 20th century. The study of tumour viruses, their oncogenes and different mechanisms employed by these viruses to subvert the growth-suppressive and pro-apoptotic functions of host tumour suppressor genes has laid the foundation of cancer biology. The human tumour viruses induce malignancies after a prolonged latency and in conjunction with other environmental and host factors. The eight known human tumour viruses contribute to nearly 10–15% of the cancers worldwide. Advancements in research on virus-related cancers offer a plethora of opportunities to fight cancer by preventing viral spread through vaccination and use of antivirals. Besides, recent developments on viral oncogenic mechanisms should allow development of novel and targeted approaches for control and treatment of virus-associated human cancers.
Effect of Transforming Viruses on Molecular Mechanisms Associated With Cancer
Journal of Cellular Physiology, 2008
Viruses have been linked to approximately 20% of all human tumors worldwide. These transforming viruses encode viral oncoproteins that interact with cellular proteins to enhance viral replication. The transcriptional and post-transcriptional effects of these viral oncoproteins ultimately result in cellular transformation. Historically, viral research has been vital to the discovery of oncogenes and tumor suppressors with more current research aiding in unraveling some mechanisms of carcinogenesis. Interestingly, since transforming viruses affect some of the same pathways that are dysregulated in human cancers, their study enhances our understanding of the multistep process of tumorigenesis. This review will examine the cellular mechanisms targeted by oncogenic human viruses and the processes by which these effects contribute to transformation. In particular, we will focus on three transforming viruses, human T-cell leukemia virus type-I, hepatitis B virus and human papillomavirus. These viruses all encode specific oncogenes that promote cell cycle progression, inhibit DNA damage checkpoint responses and prevent programmed cell death in an effort to promote viral propagation. While the transforming properties of these viruses are probably unintended consequences of replication strategies, they provide excellent systems in which to study cancer development.
A Review on Gene Involved in Cancer Development and Oncogenic Viruses
2015
Oncogenic viruses are the viruses that cause cancers in their natural hosts or experimental animal systems which are thought to be causative agents of about 15-20% of cancers. They have been broadly classified into the DNA oncogenic viruses and RNA oncogenic viruses based on the nature of the nucleic acid contain within their virion. The oncogenic DNA and RNA viruses that have been identified both in animals and humans includes retroviruses, papillomaviruses, herpesviruses and other DNA viruses. Oncogenic viruses promote cellular transformation, prompt uncontrollable cell generation and lead to development of malignant tumors. Virtually all type of normal cells may undergo the changes that eventually create tumors. For better understanding of cancer, knowing the mechanisms through which cancers produced is important. Generally this paper gives highlight about some of the gens induced cancer and related oncogenic viruses.